Method of administering bisphosphonates

Abstract

Bisphosphonates, in particular more potent N-bisphosphonates such as zoledronic acid and derivatives, can be used with satisfactory results for treatment of RA by intermittent administration, wherein the periods between bisphosphonate administrations are from about 2 months up to about 4 months, e.g. once every 3 months.

1 . A method for the treatment of rheumatoid arthritis in a patient in need of such treatment which comprises intermittently administering an effective amount of a bisphosphonate to the patient, wherein the period between administrations of bisphosphonate is from at least about 2 months up to about 4 months. 
     
     
         2 . (canceled) 
     
     
         3 . A kit for the treatment of rheumatoid arthritis comprising one or more unit doses, each comprising an effective amount of a bisphosphonate, according to a dose regimen for intermittent administration at intervals from at least about 2 months up to about 4 months to a patient in need of such treatment. 
     
     
         4 . A method according to  claim 1 , in which the bisphosphonate dosing interval is from about once every 80 days to about once every 100 days. 
     
     
         5 . A method according to  claim 1 , in which the bisphosphonate dosing interval is about once every 90 days or annual calendar quarter. 
     
     
         6 . A method according to  claim 1 , in which the bisphosphonate is a compound of formula I′ 
       
         
           
           
               
               
           
         
       
       wherein
 X is hydrogen, hydroxyl, amino, alkanoyl, or an amino group mono- or disubstituted by C 1 -C 4  alkyl; 
 R is hydrogen or C 1 -C 4  alkyl and 
 Rx′ is a side chain which contains an optionally substituted amino group, or a nitrogen containing heterocycle (including aromatic nitrogen-containing heterocycles), 
 and pharmaceutically acceptable salts thereof or any hydrate thereof. 
 
     
     
         7 . A method according to  claim 1 , in which the bisphosphonate is a compound of formula IV 
       
         
           
           
               
               
           
         
       
       wherein
 Het′″ is an imidazolyl, 2H-1,2,3-, 1H-1,2,4- or 4H-1,2,4-triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl or thiadiazolyl radical which is unsubstituted or C-mono- or di-substituted by lower alkyl, by lower alkoxy, bx phenyl which may in turn be mono- or disubstituted by lower alkyl, lower alkoxy and/or halogen, by hydroxy, by di-lower alkylamino, by lower alkylthio and/or by halogen and is N-substituted at a substitutable N-atom by lower alkyl or by phenyl-lower alkyl which may in turn be mono- or di-substituted in the phenyl moiety by lower alkyl, lower alkoxy and/or halogen, and 
 R2 is hydrogen, hydroxy, amino, lower alkylthio or halogen, 
 lower radicals having up to and including 7 C-atoms, 
 or a pharmacologically acceptable salt thereof. 
 
     
     
         8 . A method according to  claim 7 , in which the bisphosphonate is 1-hydroxy-2-(imidazol-1-yl)ethane-1,1-diphosphonic acid, or a pharmaceutically acceptable salt thereof, or any hydrate thereof. 
     
     
         9 . A method according to  claim 8  in which 5 mg doses of zoledronic acid or salt thereof (dose based on free acid) are administered once every three months.